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Nerve allografts supplemented with schwann cells overexpressing glial-cell-line–derived neurotrophic factor

Authors

  • Katherine B. Santosa MD,

    1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
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  • Nithya J. Jesuraj PhD,

    1. Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA
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  • Andreu Viader PhD,

    1. Department of Genetics, Washington University, St. Louis, Missouri, USA
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  • Matthew MacEwan BSc,

    1. Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA
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  • Piyaraj Newton BS,

    1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
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  • Daniel A. Hunter RA,

    1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
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  • Susan E. Mackinnon MD,

    1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
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  • Philip J. Johnson PhD

    Corresponding author
    1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
    • Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
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Abstract

Introduction:

We sought to determine whether supplementation of acellular nerve allografts (ANAs) with Schwann cells overexpressing GDNF (G-SCs) would enhance functional recovery after peripheral nerve injury.

Methods:

SCs expanded in vitro were infected with a lentiviral vector to induce GDNF overexpression. Wild-type SCs (WT-SCs) and G-SCs were seeded into ANAs used to repair a 14-mm nerve gap defect. Animals were harvested after 6 and 12 weeks for histomorphometric and muscle force analysis.

Results:

At 6 weeks, histomorphometry revealed that ANAs supplemented with G-SCs promoted similar regeneration compared with isograft at midgraft. However, G-SCs failed to promote regeneration into the distal stump. At 12 weeks, ANAs with G-SCs had lower maximum and specific force production compared with controls.

Conclusions:

The combined results suggest that consistent overexpression of GDNF by G-SCs trapped axons in the graft and prevented functional regeneration. Muscle Nerve, 2013

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